Methodological quality assessment is a pivotal link between primary studies and reliable evidence-based practice,and an essential pathway for operationalizing the core principles of the Guide on Methodological Standards in Pharmacoepidemiology(2nd edition).A prevalent challenge in practice,however,is the conflation of appraising methodological robustness(risk of bias assessment)with verifying reporting transparency(adherence to reporting guidelines).This paper systematically addresses this fundamental challenge,beginning with a clear distinction between the essence and boundaries of these two concepts.On this basis,the article provides a comprehensive review of mainstream quality assessment tools,covering the methodological features and evolutionary trajectory of numerous instruments for interventional(e.g.,RoB 2,ROBINS-I),observational(e.g.,NOS,the JBI/SIGN/NIH series),secondary(e.g.,AMSTAR 2),and other specific types of studies such as health economic evaluations.Furthermore,a complete case study is used to illustrate the practical application of the ROBINS-I tool.The paper's central thesis advocates for an"appraisal-informed design"philosophy,urging a conceptual shift from the retrospective critique of existing literature to the prospective quality control of new research by internalizing appraisal standards as design principles,while also exploring the emerging paradigm of artificial intelligence in assisting assessment.This paper provides a comprehensive methodological reference for researchers and practitioners to prudently select appropriate assessment tools and to conduct rigorous critical appraisals of pharmacoepidemiological evidence.

Objective To investigate the incidence and types of patient-ventilator asynchrony(PVA)in mechanically ventilated patients within the intensive care unit(ICU),and to identify associated high-risk factors,thereby providing a basis for reducing PVA,enhancing mechanical ventilation efficiency,and refining ventilation strategies.Methods A prospective observational study was conducted among patients admitted to the general ICU of the Affiliated Hospital of Guizhou Medical University from October to December 2024 who were receiving mechanical ventilation.Inclusion criteria were as follows:age ≥18 years and mechanical ventilation duration ≥12 hours.Exclusion criteria included complete controlled mechanical ventilation,palliative care or do-not-resuscitate status,and lack of informed consent.Senior respiratory therapists performed daily bedside observations of ventilator waveforms for 10～15 minutes between 08:00 and 12:00.PVA was diagnosed based on pressure-time and flow-time waveforms,with the types of PVA being recorded.Demographic and clinical data,including age,sex,body mass index(BMI),primary diagnosis,comorbidities,APACHEⅡ score at ICU admission,blood gas analysis,ventila-tion mode and parameters,analgesia and sedation status,duration of mechanical ventilation,and length of ICU stay,were collected.The incidence and types of PVA during the observation period were analyzed.Univariate and multivariate logistic regression analyses were performed to identify high-risk factors for PVA.Clinical outcomes were compared between patients with and without PVA.Results A total of 105 patients and 453 episodes of assisted mechanical ventilation waveforms were analyzed.Among these,60.95％(64/105)experienced at least one episode of PVA.Of the 453 ventilation waveforms assessed,35.76％(162/453)demonstrated PVA.The types of PVA,ranked by incidence,were as follows:cycling mismatch(12.58％,57/453),double triggering(11.92％,54/453),ineffective triggering(9.49％,43/453),flow starvation(5.30％,24/453),and exhalation flow limitation(1.77％,8/453).The incidence of PVA varied significantly across different ventilation modes:45.7％in volume-assist/control ventilation(V-A/C),38.1％in pressure-assist/control ventilation(P-A/C),42.9％in synchronized intermittent mandatory ventilation(SIMV),and 16.7％in pressure support ventilation(PSV)(P<0.001).Multi-variate logistic regression analysis revealed that the mechanical ventilation mode[reference:PSV;V-A/C:OR=4.687,95％CI:2.140～10.263,P<0.001;P-A/C:OR=2.922,95％CI:1.489～5.734,P=0.002;SIMV:OR=4.682,95％CI:1.758～12.466,P=0.002]and actual respiratory rate(OR=1.07,95％CI:1.016～1.127,P=0.011)were significant high-risk factors for PVA.Patients with PVA had a significantly longer duration of mechanical ventilation[8.21(5.35,13.91)days vs.3.00(1.96,5.71)days,P<0.001]compared to those without PVA.Conclusions PVA is commonly observed in ICU patients receiving assisted invasive mechanical ventilation,with cycling mismatch,double triggering,and ineffective triggering being the most prevalent types.The incidence of PVA tends to be lower when using the PSV mode.Clinically,real-time monitoring of patient-ventilator synchrony via ventilator waveforms,along with the optimization of ventilator modes and parameters,should be employed to minimize the occurrence of PVA and enhance the efficiency of mechanical ventilation.

Methodological quality assessment is a pivotal link between primary studies and reliable evidence-based practice,and an essential pathway for operationalizing the core principles of the Guide on Methodological Standards in Pharmacoepidemiology(2nd edition).A prevalent challenge in practice,however,is the conflation of appraising methodological robustness(risk of bias assessment)with verifying reporting transparency(adherence to reporting guidelines).This paper systematically addresses this fundamental challenge,beginning with a clear distinction between the essence and boundaries of these two concepts.On this basis,the article provides a comprehensive review of mainstream quality assessment tools,covering the methodological features and evolutionary trajectory of numerous instruments for interventional(e.g.,RoB 2,ROBINS-I),observational(e.g.,NOS,the JBI/SIGN/NIH series),secondary(e.g.,AMSTAR 2),and other specific types of studies such as health economic evaluations.Furthermore,a complete case study is used to illustrate the practical application of the ROBINS-I tool.The paper's central thesis advocates for an"appraisal-informed design"philosophy,urging a conceptual shift from the retrospective critique of existing literature to the prospective quality control of new research by internalizing appraisal standards as design principles,while also exploring the emerging paradigm of artificial intelligence in assisting assessment.This paper provides a comprehensive methodological reference for researchers and practitioners to prudently select appropriate assessment tools and to conduct rigorous critical appraisals of pharmacoepidemiological evidence.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Objective To investigate the incidence and types of patient-ventilator asynchrony(PVA)in mechanically ventilated patients within the intensive care unit(ICU),and to identify associated high-risk factors,thereby providing a basis for reducing PVA,enhancing mechanical ventilation efficiency,and refining ventilation strategies.Methods A prospective observational study was conducted among patients admitted to the general ICU of the Affiliated Hospital of Guizhou Medical University from October to December 2024 who were receiving mechanical ventilation.Inclusion criteria were as follows:age ≥18 years and mechanical ventilation duration ≥12 hours.Exclusion criteria included complete controlled mechanical ventilation,palliative care or do-not-resuscitate status,and lack of informed consent.Senior respiratory therapists performed daily bedside observations of ventilator waveforms for 10～15 minutes between 08:00 and 12:00.PVA was diagnosed based on pressure-time and flow-time waveforms,with the types of PVA being recorded.Demographic and clinical data,including age,sex,body mass index(BMI),primary diagnosis,comorbidities,APACHEⅡ score at ICU admission,blood gas analysis,ventila-tion mode and parameters,analgesia and sedation status,duration of mechanical ventilation,and length of ICU stay,were collected.The incidence and types of PVA during the observation period were analyzed.Univariate and multivariate logistic regression analyses were performed to identify high-risk factors for PVA.Clinical outcomes were compared between patients with and without PVA.Results A total of 105 patients and 453 episodes of assisted mechanical ventilation waveforms were analyzed.Among these,60.95％(64/105)experienced at least one episode of PVA.Of the 453 ventilation waveforms assessed,35.76％(162/453)demonstrated PVA.The types of PVA,ranked by incidence,were as follows:cycling mismatch(12.58％,57/453),double triggering(11.92％,54/453),ineffective triggering(9.49％,43/453),flow starvation(5.30％,24/453),and exhalation flow limitation(1.77％,8/453).The incidence of PVA varied significantly across different ventilation modes:45.7％in volume-assist/control ventilation(V-A/C),38.1％in pressure-assist/control ventilation(P-A/C),42.9％in synchronized intermittent mandatory ventilation(SIMV),and 16.7％in pressure support ventilation(PSV)(P<0.001).Multi-variate logistic regression analysis revealed that the mechanical ventilation mode[reference:PSV;V-A/C:OR=4.687,95％CI:2.140～10.263,P<0.001;P-A/C:OR=2.922,95％CI:1.489～5.734,P=0.002;SIMV:OR=4.682,95％CI:1.758～12.466,P=0.002]and actual respiratory rate(OR=1.07,95％CI:1.016～1.127,P=0.011)were significant high-risk factors for PVA.Patients with PVA had a significantly longer duration of mechanical ventilation[8.21(5.35,13.91)days vs.3.00(1.96,5.71)days,P<0.001]compared to those without PVA.Conclusions PVA is commonly observed in ICU patients receiving assisted invasive mechanical ventilation,with cycling mismatch,double triggering,and ineffective triggering being the most prevalent types.The incidence of PVA tends to be lower when using the PSV mode.Clinically,real-time monitoring of patient-ventilator synchrony via ventilator waveforms,along with the optimization of ventilator modes and parameters,should be employed to minimize the occurrence of PVA and enhance the efficiency of mechanical ventilation.

Steroid-induced osteonecrosis of femoral head (SONFH) is a disease characterized by femoral head collapse and local pain caused by excessive use of glucocorticoids. Peroxisome proliferator-activated receptor-γ (PPARγ) is mainly expressed in adipose tissue. Wnt/β-catenin, AMPK and other related signaling pathways play an important role in regulating adipocyte differentiation, fatty acid uptake and storage. Bone marrow mesenchymal cells (BMSCs) have the ability to differentiate into adipocytes or osteoblasts, and the use of hormones upregulates PPARγ expression, resulting in BMSCs biased towards adipogenic differentiation. The increase of adipocytes affects the blood supply and metabolism of the femoral head, and the decrease of osteoblasts leads to the loss of trabecular bone, which eventually leads to partial or total ischemic necrosis and collapse of the femoral head. MicroRNAs (miRNAs) are a class of short non-coding RNAs that regulate gene expression by inhibiting the transcription or translation of target genes, thereby affecting cell function and disease progression. Studies have shown that miRNAs affect the progression of SONFH by regulating PPARγ lipid metabolism-related signaling pathways. Therefore, it may be an accurate and feasible SONFH treatment strategy to regulate adipogenic-osteoblast differentiation in BMSCs by targeted intervention of miRNA differential expression to improve lipid metabolism. In this paper, the miRNA-mediated PPARγ-related signaling pathways were classified and summarized to clarify their effects on lipid metabolism in SONFH, providing a theoretical reference for miRNA targeted therapy of SONFH, and then providing scientific evidence for SONFH precision medicine.
MicroRNAs/physiology* ; PPAR gamma/metabolism* ; Femur Head Necrosis/metabolism* ; Humans ; Signal Transduction/physiology* ; Lipid Metabolism/physiology* ; Animals ; Cell Differentiation ; Mesenchymal Stem Cells/cytology* ; Glucocorticoids/adverse effects*

This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

This paper explored the specific mechanism of ginsenoside Rg_1 in regulating mitochondrial fusion through the neurogenic gene Notch homologous protein 1(Notch1) pathway to alleviate hypoxia/reoxygenation(H/R) injury in HL-1 cells. The relative viability of HL-1 cells after six hours of hypoxia and two hours of reoxygenation was detected by cell counting kit-8(CCK-8). The lactate dehydrogenase(LDH) activity in the cell supernatant was detected by the lactate substrate method. The content of adenosine triphosphate(ATP) was detected by the luciferin method. Fluorescence probes were used to detect intracellular reactive oxygen species(Cyto-ROS) levels and mitochondrial membrane potential(ΔΨ_m). Mito-Tracker and Actin were co-imaged to detect the number of mitochondria in cells. Fluorescence quantitative polymerase chain reaction and Western blot were used to detect the mRNA and protein expression levels of Notch1, mitochondrial fusion protein 2(Mfn2), and mitochondrial fusion protein 1(Mfn1). The results showed that compared with that of the control group, the cell activity of the model group decreased, and the LDH released into the cell culture supernatant increased. The level of Cyto-ROS increased, and the content of ATP decreased. Compared with that of the model group, the cell activity of the ginsenoside Rg_1 group increased, and the LDH released into the cell culture supernatant decreased. The level of Cyto-ROS decreased, and the ATP content increased. Ginsenoside Rg_1 elevated ΔΨ_m and increased mitochondrial quantity in HL-1 cells with H/R injury and had good protection for mitochondria. After H/R injury, the mRNA and protein expression levels of Notch1 and Mfn1 decreased, while the mRNA and protein expression levels of Mfn2 increased. Ginsenoside Rg_1 increased the mRNA and protein levels of Notch1 and Mfn1, and decreased the mRNA and protein levels of Mfn2. Silencing Notch1 inhibited the action of ginsenoside Rg_1, decreased the mRNA and protein levels of Notch1 and Mfn1, and increased the mRNA and protein levels of Mfn2. In summary, ginsenoside Rg_1 regulated mitochondrial fusion through the Notch1 pathway to alleviate H/R injury in HL-1 cells.
Ginsenosides/pharmacology* ; Receptor, Notch1/genetics* ; Signal Transduction/drug effects* ; Mice ; Animals ; Mitochondrial Dynamics/drug effects* ; Mitochondria/metabolism* ; Cell Line ; Reactive Oxygen Species/metabolism* ; Oxygen/metabolism* ; Cell Hypoxia/drug effects* ; Cell Survival/drug effects* ; Membrane Potential, Mitochondrial/drug effects* ; Humans

Testicular histology based on testicular biopsy is an important factor for determining appropriate testicular sperm extraction surgery and predicting sperm retrieval outcomes in patients with azoospermia. Therefore, we developed a deep learning (DL) model to establish the associations between testicular grayscale ultrasound images and testicular histology. We retrospectively included two-dimensional testicular grayscale ultrasound from patients with azoospermia (353 men with 4357 images between July 2017 and December 2021 in The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China) to develop a DL model. We obtained testicular histology during conventional testicular sperm extraction. Our DL model was trained based on ultrasound images or fusion data (ultrasound images fused with the corresponding testicular volume) to distinguish spermatozoa presence in pathology (SPP) and spermatozoa absence in pathology (SAP) and to classify maturation arrest (MA) and Sertoli cell-only syndrome (SCOS) in patients with SAP. Areas under the receiver operating characteristic curve (AUCs), accuracy, sensitivity, and specificity were used to analyze model performance. DL based on images achieved an AUC of 0.922 (95% confidence interval [CI]: 0.908-0.935), a sensitivity of 80.9%, a specificity of 84.6%, and an accuracy of 83.5% in predicting SPP (including normal spermatogenesis and hypospermatogenesis) and SAP (including MA and SCOS). In the identification of SCOS and MA, DL on fusion data yielded better diagnostic performance with an AUC of 0.979 (95% CI: 0.969-0.989), a sensitivity of 89.7%, a specificity of 97.1%, and an accuracy of 92.1%. Our study provides a noninvasive method to predict testicular histology for patients with azoospermia, which would avoid unnecessary testicular biopsy.
Humans ; Male ; Azoospermia/diagnostic imaging* ; Deep Learning ; Testis/pathology* ; Retrospective Studies ; Adult ; Ultrasonography/methods* ; Sperm Retrieval ; Sertoli Cell-Only Syndrome/diagnostic imaging*